Standard closed-chest cardiopulmonary resuscitation (CPR) produces levels of coronary blood flow that are inadequate to maintain aerobic myocardial metabolism during ventricular fibrillation. The studies outlined in this application will examine hemodynamic, pharmacologic, mechanical, and biochemical factors relevant to maintenance or improvement of coronary blood flow and myocardial oxygenation during CPR. The first group of experiments will evaluate the hemodynamic and metabolic effects of endogenous and exogenous catecholamines during experimental resuscitation. Specific projects are designed to determine the mechanisms by which exogenous epinephrine increases arterial and coronary perfusion pressures during CPR; the extent to which endogenous catecholamines released during CPR influence myocardial oxygen requirements during ventricular fibrillation; whether myocardial oxygenation during CPR can be improved by alpha-adrenergic vasoconstriction, alone or in combination with beta-adrenergic blockade; and whether the combined use of an alpha-adrenergic agonist and a beta-adrenergic antagonist during CPR can increase the likelihood of successful defibrillation and reduce post-resuscitation left ventricular dysfunction due to ischemic myocardial injury. A separate group of experiments will examine the mechanisms by which volume loading increases arterial pressure and forward blood flow during CPR; test the hypothesis that increased forward flow results primarily from decreased resistance in nonvital beds; and determine whether coronary perfusion pressure and blood flow during CPR can be augmented by a combination of blood volume expansion and pharmagologic vasoconstriction. The experiments in Section 3 will analyze time-concentration and time-activity relationships of pharmacologic agents administered during CPR; determine the extent to which these relationships are influenced by the time at which drugs are administered after the onset of CPR, and by pharmacologic alpha-adrenergic vasoconstriction; and examine the dose-response relationships between vasoconstricting agents and coronary perfusion pressure during CPR. It is hoped that the results of these studies will both provide insight into the basic mechanisms of action and metabolic consequences of interventions aimed at improving myocardial oxygenation during CPR, and establish a rational framework for the application of these interventions during attempted resuscitation.